Bupropion-SR in treatment of social phobia.

A 12-week, open label flexible dosing study was conducted to evaluate the efficacy of bupropion-SR in the treatment of generalized social phobia. The primary outcome measures include the Clinical Global Impression of Improvement (CGI-I) and the Brief Social Phobia Rating Scale (BSPS). A total of 18 subjects were enrolled. Five of the ten subjects who completed all 12 weeks were considered as responders. Response to treatment was defined as a CGI-I score of 1 or 2, ("much improved" or "very much improved," respectively) and a > 50% decrease in BSPS score. The final doses for the completers ranged between 200 and 400 mg/day (mean 366 +/- 68 mg/day). The medication was generally well tolerated. Findings from this open-label trial suggest that bupropion-SR may be useful in treating generalized social phobia.

Evaluation of the efficacy, safety and physiological effects of fluvoxamine in social phobia.

There is no US Food and Drug Administration (FDA) approved treatment for social phobia although data suggest efficacy for several drug classes, including beta-blockers, benzodiazepines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). The SSRIs are particularly attractive due to their favourable tolerance and safety profile. An open label trial of fluvoxamine was conducted to evaluate its efficacy and safety in the treatment of social phobia (DSM-III-R) and to assess physiological changes that may accompany treatment. Fifteen non-depressed patients, aged 22-44 years (mean 31.6 years), entered the study. A 5-min performance task (public speaking simulation) preceded and concluded the active treatment period. Cardiovascular monitoring was performed during this time and blood sampled for plasma cortisol and steady-state plasma fluvoxamine concentration (at week 7). Ten patients (5 men and 5 women) completed an active 6 week treatment period of flexible dosing (50-150 mg/day). Five patients failed to complete the study due to drowsiness (n = 2), nausea (n = 1), or were lost to follow-up (n = 2). Analysis of clinical ratings indicated a statistically significant decrease in all scales from baseline to week 7 at the conclusion of the active treatment period. Clinical benefits were still evident at follow-up 1 week after drug discontinuation. Neither physiological effects nor plasma drug concentration correlated with clinical change. Fluvoxamine appeared to be effective and well tolerated in completers. Randomized clinical trials are needed to further demonstrate the efficacy of fluvoxamine in the treatment of social phobia.

Abnormal peripheral benzodiazepine receptor density associated with generalized social phobia.

BACKGROUND: Peripheral benzodiazepine receptors (PBRs) are involved in regulating stress responses. Abnormally low numbers of platelet PBRs have been found in patients with panic disorder, posttraumatic stress disorder, and generalized anxiety disorder, but not in patients with obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). The purpose of this study was to evaluate the PBR density on platelets from patients with generalized social phobia (GSP). METHODS: The density (Bmax) and dissociation constant (Kd) of platelet PBRs was determined for 53 medication-free patients with GSP and an equal number of control subjects (NC). RESULTS: The GSP group was found to have a significantly lower PBR Bmax than the NC group (GSP = 2764 +/- 1242 vs. NC = 4327 +/- 1850 fmol/mg protein, df = 1,100, F = 22.7, p = .00001). CONCLUSIONS: GSP shares this PBR abnormality with some other anxiety disorders but not with OCD or MDD. PBRs may play a role in the pathophysiology of some anxiety disorders.

Clinical psychopharmacy consultations: acceptance of recommendations on an adult inpatient psychiatric unit.

A retrospective chart review of consultations performed by a clinical pharmacist practicing in an adult psychiatric hospital was conducted. Data during the first 12 months of the service were collected from consultation reports, progress notes, physician's orders, laboratory data, and discharge summaries. Twenty-nine consultations were performed, resulting in a total of 135 recommendations. Of those, 125 were assessed and categorized. Of the recommendations, 113 (90.4%) were medication related and 12 (9.6%) were non-medication related. From the 125 recommendations, 99 (79.2%) were implemented and 26 (20.8%) were not. Particular categories of recommendations were also analyzed and had individual implementation rates ranging from 33.3% to 100%. Clinical pharmacists have previously documented their positive impact on patient care in a variety of settings, including psychopharmacy. The majority of recommendations made in this study were medication related with an overall implementation rate of 79%. This report illustrates the influence the clinical pharmacist has on the drug therapy of the psychiatric patient.

Venlafaxine: a structurally unique and novel antidepressant.

OBJECTIVE: To introduce the new antidepressant venlafaxine. Basic pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, dosing guidelines, and therapeutic considerations. The article also discusses several pharmacotherapy issues and how venlafaxine compares with other available antidepressants. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: As this is a relatively new agent, all available clinical trials were reviewed. DATA EXTRACTION: All clinical trials that were available prior to submission for publication were reviewed. Preliminary trials and unpublished reports were not reviewed. DATA SYNTHESIS: Venlafaxine hydrochloride is a structurally novel agent that has recently been approved in the US for the treatment of depression. This unique antidepressant blocks neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. Venlafaxine and its major active metabolite, O-desmethylvenlafaxine, exhibit linear kinetics with an elimination half-life of 5 and 11 hours, respectively. Venlafaxine has been evaluated in 7 clinical trials for the treatment of depression. These have consisted of 2 open trials, 3 double-blind, placebo-controlled trials, and 2 double-blind trials where venlafaxine was compared with trazodone and imipramine. All 7 trials have established efficacy for venlafaxine using standard psychiatric rating scales to measure change of depressive symptoms. The usual daily dosage ranges from 75 to 225 mg/d in 2 to 3 divided doses, with a maximum daily dosage of 375 mg/d. The drug's adverse effect profile differs somewhat from other more specific serotonin reuptake inhibitors in that it appears to cause dry mouth, somnolence, and elevated blood pressure as well as nausea, headache, and dizziness. CONCLUSIONS: Although venlafaxine has recently become available for use as an antidepressant in the US, few clinical trials have been conducted to help the practitioner evaluate its place in the treatment of depression. There are no comparative trials of venlafaxine with the serotonin specific reuptake inhibitor antidepressants, which are rapidly becoming the newest comparative standard. The clinical place for venlafaxine in the treatment of depression has yet to be determined.

Substance abuse and bipolar affective disorder.

This interview study was conducted to explore the onset, course, and features of bipolar affective disorder complicated by substance abuse. Forty-four patients with a diagnosis of bipolar affective disorder were interviewed using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scale for Depression, Young Mania Rating Scale, and a questionnaire concerning psychiatric history. Current substance users averaged twice as many hospitalizations for mood problems. The age of onset of mood problems for substance users was significantly earlier than that of the nonusers (p < or = .05). Substance users were four times as likely to have other comorbid axis I disorders (p < or = .05) and twice as likely to have dysphoric mania at time of interview. This preliminary study suggests that individuals with bipolar affective disorder complicated by substance abuse may have more hospitalizations, a higher incidence of dysphoric mania, earlier onset of mood problems, and more comorbid axis I disorders.

Pharmacologic management of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is an intriguing, difficult problem characterized by anxiety-producing intrusive thoughts and performance of anxiety-reducing rituals. Current evidence suggests that OCD may be associated with dysregulation of serotonin and dopamine neurotransmission. Numerous early studies involving the serotonin-specific reuptake inhibitor clomipramine led to the formulation of this hypothesis. Positive results with clomipramine initiated further research with other serotonin-specific reuptake inhibitors, such as fluoxetine, fluvoxamine, sertraline, and serotonergic agents such as buspirone and trazodone. Findings from a number of clinical trials suggest that drugs that inhibit serotonin reuptake or affect serotonergic transmission in other ways are of clear benefit in the treatment of OCD. These drugs may be more effective for obsessive thoughts than for compulsive rituals. Effective pharmacotherapy can dramatically decrease obsessive-compulsive symptoms and improve the patient's quality of life.

A prediction model for identifying alcohol withdrawal seizures.

A retrospective review of alcohol withdrawal seizures was performed at a private chemical-dependence treatment facility to help identify patients who were at high risk for having a seizure. Patients were identified by two means: controlled substance records were reviewed to determine patients having received intramuscular phenobarbital, and patient charts were reviewed for all patients with a discharge diagnosis of a seizure disorder. Two thousand and one patient records were reviewed; alcohol withdrawal seizure patients were identified. Twenty-eight randomly selected nonseizure patient records served as controls. The statistical test consisted of a discriminant function analysis. The data yielded a statistically significant predictive model for alcohol withdrawal seizures based on six interdependent patient variables which will be helpful in treating future patients undergoing alcohol withdrawal.

Cardiovascular effects of imipramine, fluvoxamine, and placebo in depressed outpatients.

BACKGROUND: The data presented represent cardiovascular parameters collected from one site of a larger, multicenter, double-blind, placebo-controlled, 6-week outpatient efficacy study of the serotonin uptake inhibitor fluvoxamine in depressed outpatients. METHOD: In this smaller study, we compared fluvoxamine (N = 17) to the prototypic antidepressant, imipramine (N = 14), and to placebo (N = 15). Specific parameters investigated were drug effects on postural pulse and blood pressure changes and ECG parameters including PR, QRS, and QTc intervals and ventricular heart rate. RESULTS: Fluvoxamine had few effects on measured parameters. Imipramine produced statistically significant changes on all measures; placebo had no effects on cardiac measures. CONCLUSION: Our data support that fluvoxamine, in a sample of healthy depressed outpatients, has little effect on cardiovascular function. Further study and clinical experience with this drug will be necessary before the full extent of its cardiac profile is known.

Effect of fluvoxamine, imipramine and placebo on catecholamine function in depressed outpatients.

Many of the specific serotonin reuptake inhibitors appear to have some effect on noradrenergic function. Fluvoxamine is one of the newer agents and its specificity has not been fully assessed. Depressed patients participating in a study comparing the efficacy of fluvoxamine with imipramine and placebo collected 24 hour urine samples (N = 38) and had plasma samples drawn (N = 38) prior to and after 6 weeks of double blind treatment. Urine samples were analyzed for 24 hour output of MHPG, VMA, NMN, MN and HVA. Plasma samples were analyzed for NE levels. Imipramine treatment produced a reduction in urinary MHPG, an increase in the ratio of NMN to MHPG plus VMA, and a trend towards an increase in plasma NE which was significantly different than the effects seen in the fluvoxamine and placebo groups. There was an additional finding in the imipramine group of a significant correlation between percentage change in plasma NE and clinical improvement. Fluvoxamine treatment, on the other hand, produced no clear effect on any measure of noradrenergic function and the antidepressant efficacy of fluvoxamine was unrelated to any noradrenergic variable. These findings lend support to the hypothesis that fluvoxamine does not have significant effects on noradrenergic function.

Preliminary report: placebo-controlled, double-blind study of the clinical and metabolic effects of desipramine in panic disorder.

Fifty-six males and females with panic disorder with or without agoraphobia participated in a 12-week, placebo-controlled treatment study of the efficacy of desipramine (DMI). Twenty-six of 28 patients receiving DMI completed the study; 17 of 28 placebo (PBO) recipients completed 12 weeks. Patients receiving DMI responded significantly better than did PBO recipients as measured by Hamilton Anxiety Scale (HAM-A) and global phobia ratings, with a trend toward greater global improvement, but no between-group differences on panic attack frequency were discerned. By Week 12, 22 of 26 (85%) DMI patients were panic-free; 13 of 17 (76%) PBO patients were panic-free. Resting metabolic rate (RMR) was tested on a subset of the patients. Patients receiving DMI showed no effects on RMR or thyroid indices but lost a significant amount of weight; the PBO recipients exhibited no weight loss or RMR effects. In this study, the high PBO response rate obscured treatment group differences on some measures. This study underscores the need for placebo comparisons in treatment studies. In summary, DMI appears to be an effective treatment for panic disorder. DMI appears to have little effect on RMR; a slight but significant weight loss was observed in the DMI but not PBO group.

Lithium side effects in the medically ill.

OBJECTIVE: This review will include the general pharmacology of lithium and discuss its effects on various organ systems, with emphasis on the medically ill patient as well as the geriatric patient with multiple medical problems. METHODS: A full literature review on the side effects of lithium was performed. Attention is focused on the medically ill and possible drug interactions. RESULTS: This review points to the numerous problems which can result in toxicity in the medically ill or the geriatric patient. CONCLUSION: Serious side effects can be avoided with proper drug monitoring and knowledge of potential drug interactions.

The clinical usefulness of lithium as an antidepressant.

Much attention has been directed toward the use of lithium in bipolar depressive illness (manic-depressive illness), but fewer studies have evaluated lithium's efficacy in unipolar depressive disorders. This paper critically reviews the literature dealing with the use of lithium for the treatment of acute unipolar depression as well as for prophylaxis against future depressive episodes. Differences in study design, entry criteria, serum lithium level, dose, patient population, and diagnosis are highlighted; these variations help explain some of the controversy surrounding the use of lithium in unipolar depression. The available information indicates that lithium should be seriously considered as an effective alternative for the treatment of unipolar depression when other antidepressant medications are ineffective or contraindicated.